The present work seeks to advance quantitative understanding of semicircular canal biomechanics under both physiological and pathological conditions with the goals of 1) improving the assessment and treatment of benign paroxysmal positional vertigo (BPPV), 2) quantifying the micromechanical substrates of angular motion sensation and 3) providing a new understanding of the role of active hair- bundle motility in sensory transduction by the semicircular canals. First, results will detail pathological biomechanical and neural inputs to the brain under conditions of experimentally induced canalithiasis (canalolithiasis). Experiments will focus on amplification that may occur as particles move from the ampulla to the canal duct and the attenuation that may occur as small particles move from the center of the duct to the canal wall. Second, experimental results will determine micromechanical contributions underlying the neural representation of angular head movements and the diverse neural code transmitted from the semicircular canals to the brain. Third, the data will determine the role of active hair cell/bundle motility in the sensitivity and selectivity of angular motion sensation. The action of the efferent vestibular system and, separately, electrical polarization of the endolymph on hair-cell and micromechanical responses will also be determined. Results are expected to have immediate relevance to health and the human condition through the assessment and treatment of classical and non-classical BPPV as well as long term significance enhancing basic understanding of semicircular canal micromechanics, hair-cell active processes in transduction and efferent control of motion sensation by the brain.
Disorders of the vestibular system are debilitating and common, afflicting approximately 30% of the population over the age of 65 and accounting for over 5 million patient visits to the physician each year in the U.S. alone [22, 23]. The present application is directly relevant to the biomechanical substrates and pathological afferent neural responses associated with benign paroxysmal positional vertigo and conditions affecting cupular mechanics, hair-bundle mechanics and hair-cell mechano- electrical transduction (MET). Results are expected to lead to a more complete quantitative description of how canalithiasis alters afferent inputs to the brain, and to improved diagnostic procedures and therapeutic approaches for canalithiasis. In the longer term, knowledge to be gained regarding micromechanical substrates of adaptation and the role of hair bundle motility will contribute to our fundamental understanding of how the neural code is generated in health and how it is altered in disease.
|Zhu, Hong; Tang, Xuehui; Wei, Wei et al. (2014) Input-output functions of vestibular afferent responses to air-conducted clicks in rats. J Assoc Res Otolaryngol 15:73-86|
|Tran, Vy M; Kuberan, Balagurunathan (2014) Synthesis of fluorophore-tagged xylosides that prime glycosaminoglycan chains. Bioconjug Chem 25:262-8|
|Highstein, Stephen M; Holstein, Gay R; Mann, Mary Anne et al. (2014) Evidence that protons act as neurotransmitters at vestibular hair cell-calyx afferent synapses. Proc Natl Acad Sci U S A 111:5421-6|
|Dharia, Sameera; Rabbitt, Richard D (2011) Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation. PLoS One 6:e17363|
|Dittami, Gregory M; Rajguru, Suhrud M; Lasher, Richard A et al. (2011) Intracellular calcium transients evoked by pulsed infrared radiation in neonatal cardiomyocytes. J Physiol 589:1295-306|
|Rajguru, Suhrud M; Richter, Claus-Peter; Matic, Agnella I et al. (2011) Infrared photostimulation of the crista ampullaris. J Physiol 589:1283-94|
|Rabbitt, Richard D; Boyle, Richard; Highstein, Stephen M (2010) Mechanical amplification by hair cells in the semicircular canals. Proc Natl Acad Sci U S A 107:3864-9|
|Rabbitt, Richard D; Breneman, Kathryn D; King, Curtis et al. (2009) Dynamic displacement of normal and detached semicircular canal cupula. J Assoc Res Otolaryngol 10:497-509|
|Breneman, Kathryn D; Brownell, William E; Rabbitt, Richard D (2009) Hair cell bundles: flexoelectric motors of the inner ear. PLoS One 4:e5201|
|Boyle, Richard; Rabbitt, Richard D; Highstein, Stephen M (2009) Efferent control of hair cell and afferent responses in the semicircular canals. J Neurophysiol 102:1513-25|
Showing the most recent 10 out of 17 publications